Adverse systemic reactions associated with the use of topical ophthalmic timolol, chloramphenicol, phenylephrine and cyclopentolate are surveyed, with special emphasis on precautions and contraindications for these ophthalmic drug preparations. Systemic reactions secondary to timolol, a beta-adrenergic antagonist indicate that it should be used with caution in patients with asthma or a history of asthma, chronic obstructive pulmonary disease or cardiovascular disease and in those patients receiving systemic administration of beta-blockers or verapamil. Because significant blood dyscrasias or aplastic anaemia have been reported following topical ophthalmic chloramphenicol, the only absolute indication in ocular conditions is an organism that is resistant to all other antibiotics. Both 2.5% and 10% phenylephrine have been associated with cardiovascular effects and should be used with caution in selected patients on monoamine oxidase inhibitors, tricyclic antidepressants or atropine or in those with hypertension, advanced arteriosclerotic changes, aneurysms, orthostatic hypotension, long-standing insulin-dependent diabetes and in children with low bodyweights. Central nervous system toxicity secondary to cyclopentolate is dose-related and can be avoided by use of minimal concentrations and avoidance of unnecessary repetition of administration. Occlusion of the nasolacrimal passage with finger pressure immediately after instillation of any eyedrop also decreases the amount of drug that is absorbed systemically.